散结灵胶囊治疗乳腺增生的效应机制研究
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摘要
目的研究散结灵胶囊治疗乳腺增生的效应机制。方法通过3种实验进行综合评价。①将105只雌性SD大鼠分为随机分为空白组、模型组、三苯氧胺组(0.004 g/kg)、桂枝茯苓组(0.279 g/kg)、散结灵高剂量组(0.72 g/kg)、散结灵中剂量组(0.36 g/kg)、散结灵低剂量组(0.18 g/kg),每组15只。除空白组外,其余各组均制备大鼠乳腺增生模型。于造模成功后,各给药组分别经口灌胃给予相应剂量的药物,均1次/d,连续30 d。末次灌胃结束后,测量各组大鼠第二对乳头直径和乳头高度;腹主动脉取血,测定血清中雌二醇(E_2)、孕酮(P)、催乳素(PRL)水平;大鼠第二对乳腺组织取材,光镜下观察其组织形态学变化。②将72只雄性SD大鼠随机分为空白组、模型组、复方丹参组(0.288 g/kg)、散结灵高剂量组(0.72 g/kg)、散结灵中剂量组(0.36 g/kg)、散结灵低剂量组(0.18 g/kg),每组12只。各给药组分别经口灌胃给予相应剂量的药物,均1次/d,连续7 d。除空白组外,各组在末次灌胃后30 min多点皮下注射肾上腺素制备大鼠急性血瘀模型,处置后禁食。第8天各组大鼠腹主动脉取血,测定全血黏度和血浆凝血酶原时间(PT)和纤维蛋白原(FIB)含量。③将60只ICR小鼠(雌雄各半)随机分为模型组、阿司匹林组(0.3 g/kg)、散结灵高剂量组(1.08 g/kg)、散结灵中剂量组(0.54 g/kg)、散结灵低剂量组(0.27 g/kg),每组12只。各给药组小鼠分别经口灌胃给予相应剂量的药物,均1次/d,连续5 d。末次灌胃后1 h,于小鼠腹腔注射0.7%冰醋酸生理盐水溶液,观察小鼠15 min内出现扭体反应的次数及扭体反应潜伏期。结果散结灵各组大鼠乳头直径、乳头高度及散结灵高、中剂量组大鼠血清E_2和PRL水平均明显低于模型组(P均<0.05),乳腺小叶数量增多、腺泡及导管大量增生、腺泡扩张并且分泌旺盛等乳腺增生病理组织学变化明显轻于模型组。散结灵胶囊各组大鼠全血低切黏度明显低于模型组(P均<0.05);散结灵高剂量组大鼠血浆PT明显长于模型组(P<0.05),血浆FIB含量明显低于模型组(P<0.05)。散结灵各组小鼠扭体次数明显少于模型组(P均<0.05),散结灵低、中剂量组小鼠扭体反应潜伏期明显长于模型组(P均<0.05)。结论散结灵胶囊具有较好的治疗乳腺增生和活血化瘀、镇痛作用,其中下调血清E_2和PRL水平可能是该药效应机制的关键环节。
Objective It is to study the effect mechanism of Sanjieling Capsule on hyperplasia of mammary glands. Methods Comprehensive evaluation was carried out by three experiments. ① 105 female SD rats were randomly divided into blank group, model group, tamoxifen group(0.004 g/kg), Guizhi Fuling group(0.279 g/kg), and Sanjieling high dose group(0.72 g/kg), medium dose group(0.36 g/kg) and low dose group(0.18 g/kg), 15 rats in each group. Rat mammary gland hyperplasia models were prepared in all the groups except the blank group. After the successful modeling, each drug-administered group was given the corresponding dose of the drug by oral gavage, once a day for 30 days. At the end of the last gavage, the second pair of nipple diameters and nipple heights of each group were measured. Blood was taken from the abdominal aorta to determine the levels of estradiol(E_2), progesterone(P) and prolactin(PRL) in the serum. The second pair of mammary gland tissues were taken from the rats, and the histomorphological changes were observed under light microscope. ②72 male Sprague-Dawley rats were randomly divided into blank group, model group, compound Danshen group(0.288 g/kg), Sanzhiling high dose group(0.72 g/kg), medium dose group(0.36 g/kg), low dose group(0.18 g/kg), 12 rats in each group. Each drug-administered group was given the corresponding dose of the drug by oral gavage, once a day for 7 days. Except the blank group, the acute blood stasis model of rats was prepared by subcutaneous injection of epinephrine 30 min after the last gavage, and fasted after treatment. On the 8 th day, blood was taken from the abdominal aorta of each group, and the whole blood viscosity and plasma prothrombin time(PT) and fibrinogen(FIB) content were measured. ③ 60 ICR mice(male and female) were randomly divided into model group, aspirin group(0.3 g/kg), Sanzhiling high dose group(1.08 g/kg), medium dose group(0.54 g/kg), low dose group(0.27 g/kg), 12 mice in each group. The mice in each administration group were given the corresponding doses of the drugs by oral gavage, once a day for 5 days. One hour after the last gavage, the mice were intraperitoneally injected with 0.7% glacial acetic acid saline solution to observe the number of writhing reactions and the latency of writhing reaction within 15 min. Results The nipple diameter, nipple height of the rats in every Sanjieling group and the levels of serum E_2 and PRL in high dose and middle dos group were significantly lower than those in the model group(P<0.05), and the number of mammary glands increased, the histopathological changes of mammary gland hyperplasia such as massive hyperplasia, acinar dilatation and exuberant secretion were significantly lighter than the model group. The low-cut viscosity of whole blood in the rats of Sanjieling groups was significantly lower than that in the model group(P<0.05). The plasma PT of the high dose group was significantly longer and the plasma FIB content was significantly lower than that of the model group(P<0.05). The number of writhing in the mice of Sanzhiling groups was significantly less than that in the model group(P<0.05), the latency of writhing reaction in the low dose and middle dose groups was significantly longer than that in the model group(P<0.05). Conclusion Sanjieling capsule for improving blood stasis and analgesia has better therapeutic effect on hyperplasia of mammary gland. The down-regulation of serum E_2 and PRL levels may be the key link of the drug effect mechanism.
Objective It is to study the effect mechanism of Sanjieling Capsule on hyperplasia of mammary glands. Methods Comprehensive evaluation was carried out by three experiments. ① 105 female SD rats were randomly divided into blank group, model group, tamoxifen group(0.004 g/kg), Guizhi Fuling group(0.279 g/kg), and Sanjieling high dose group(0.72 g/kg), medium dose group(0.36 g/kg) and low dose group(0.18 g/kg), 15 rats in each group. Rat mammary gland hyperplasia models were prepared in all the groups except the blank group. After the successful modeling, each drug-administered group was given the corresponding dose of the drug by oral gavage, once a day for 30 days. At the end of the last gavage, the second pair of nipple diameters and nipple heights of each group were measured. Blood was taken from the abdominal aorta to determine the levels of estradiol(E_2), progesterone(P) and prolactin(PRL) in the serum. The second pair of mammary gland tissues were taken from the rats, and the histomorphological changes were observed under light microscope. ②72 male Sprague-Dawley rats were randomly divided into blank group, model group, compound Danshen group(0.288 g/kg), Sanzhiling high dose group(0.72 g/kg), medium dose group(0.36 g/kg), low dose group(0.18 g/kg), 12 rats in each group. Each drug-administered group was given the corresponding dose of the drug by oral gavage, once a day for 7 days. Except the blank group, the acute blood stasis model of rats was prepared by subcutaneous injection of epinephrine 30 min after the last gavage, and fasted after treatment. On the 8 th day, blood was taken from the abdominal aorta of each group, and the whole blood viscosity and plasma prothrombin time(PT) and fibrinogen(FIB) content were measured. ③ 60 ICR mice(male and female) were randomly divided into model group, aspirin group(0.3 g/kg), Sanzhiling high dose group(1.08 g/kg), medium dose group(0.54 g/kg), low dose group(0.27 g/kg), 12 mice in each group. The mice in each administration group were given the corresponding doses of the drugs by oral gavage, once a day for 5 days. One hour after the last gavage, the mice were intraperitoneally injected with 0.7% glacial acetic acid saline solution to observe the number of writhing reactions and the latency of writhing reaction within 15 min. Results The nipple diameter, nipple height of the rats in every Sanjieling group and the levels of serum E_2 and PRL in high dose and middle dos group were significantly lower than those in the model group(P<0.05), and the number of mammary glands increased, the histopathological changes of mammary gland hyperplasia such as massive hyperplasia, acinar dilatation and exuberant secretion were significantly lighter than the model group. The low-cut viscosity of whole blood in the rats of Sanjieling groups was significantly lower than that in the model group(P<0.05). The plasma PT of the high dose group was significantly longer and the plasma FIB content was significantly lower than that of the model group(P<0.05). The number of writhing in the mice of Sanzhiling groups was significantly less than that in the model group(P<0.05), the latency of writhing reaction in the low dose and middle dose groups was significantly longer than that in the model group(P<0.05). Conclusion Sanjieling capsule for improving blood stasis and analgesia has better therapeutic effect on hyperplasia of mammary gland. The down-regulation of serum E_2 and PRL levels may be the key link of the drug effect mechanism.
引文
[1] 刘靖,靳小磊,耿刚. 乳腺增生病发病因素的分析[J]. 内蒙古中医药,2010,29(5):121-124
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[8] 李彩文,白丽萍,李贺兰,等. 乳结消丸对乳腺增生病大鼠性激素水平影响的实验研究[J]. 现代中西医结合杂志,2010,19(29):3708-3709
[9] 郭新荣,张卫华,李树兰. 针刺对乳腺增生模型大鼠卵巢垂体轴性激素调节作用的影响[J]. 山东中医杂志,2013,32(7):485-519
[10] 唐汉钧. 乳腺增生病辩证论治述要[J]. 上海中医药杂志,2007,41(6):49-51
[11] 胡升芳,陈红风. 乳腺增生病中医辨证客观化指标探索[J]. 上海中医药大学学报,2004,18(4):14-17
[12] 郭文芳,裴晓华. 裴晓华教授治疗乳癖七法探微[J]. 新中医,2012,44(10):155-156
[2] 徐春红. 乳腺增生病的流行病学综述[J]. 北方药学,2013,10(12):92-93
[3] 余成浩,李文军,王帅,等. 复方美登木片防治大鼠乳腺增生的研究[J]. 中药药理与临床,2012,28(2):137-139
[4] 和岚,蒋文跃,毛腾敏. 注射肾上腺素模拟“气滞”复制急、慢性血瘀模型初探[J]. 中国中西医结合杂志,2004,24(3):244-246
[5] 徐淑云,卞如濂,陈修. 药理实验方法学[M]. 北京:人民卫生出版社出版,2003:882
[6] 孙二虎,陆澄,黄艳,等. 丹皮酚对乳腺增生病模型大鼠体内激素及激素受体表达的影响[J]. 广西医科大学学报,2012,29(2):200-202
[7] 苏富芳,饶媛媛. 乳腺增生的现状成因研究及针对性预防措施[J]. 中国实验诊断学,2011,15(8):1360-1361
[8] 李彩文,白丽萍,李贺兰,等. 乳结消丸对乳腺增生病大鼠性激素水平影响的实验研究[J]. 现代中西医结合杂志,2010,19(29):3708-3709
[9] 郭新荣,张卫华,李树兰. 针刺对乳腺增生模型大鼠卵巢垂体轴性激素调节作用的影响[J]. 山东中医杂志,2013,32(7):485-519
[10] 唐汉钧. 乳腺增生病辩证论治述要[J]. 上海中医药杂志,2007,41(6):49-51
[11] 胡升芳,陈红风. 乳腺增生病中医辨证客观化指标探索[J]. 上海中医药大学学报,2004,18(4):14-17
[12] 郭文芳,裴晓华. 裴晓华教授治疗乳癖七法探微[J]. 新中医,2012,44(10):155-156